1999 Fiscal Year Final Research Report Summary
Gene therapy for cancer using the gone gun system
| Project/Area Number |
09557094
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
General surgery
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| Research Institution | Tohoku University |
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Principal Investigator |
SUNAMURA Makoto Tohoku University, Hospital, Lecture, 医学部附属病院, 講師 (10201584)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBUYA Kazuhiko Tohoku University, Hospital, Research Associate, 医学部附属病院, 助手 (70260429)
HAMADA Hirofumi Sapporo Medical College, Medicine, Professor, 医学部, 教授 (00189614)
SATO Masaaki Tohoku University, Engineering, Professor, 大学院・工学研究科, 教授 (30111371)
SHIMAMURA Hiromune Tohoku University, Hospital, Research Associate, 医学部附属病院, 助手 (70312585)
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| Project Period (FY) |
1997 – 1999
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| Keywords | gene gun / gene therapy / cancer / angiogenesis / IL-12 |
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| Research Abstract |
In order to establish a gene therapy system without vectors, we checked the efficacy of gene gun for gene transduction. Although we could confirm the expression of LacZ gene in pancreatic cancer cells, the transduction efficacy was very low. It is important to choose the suitable gene which can express the efficient anti-tumor effect with low concentration for gene gun System. As an anti-tumor agent, Interleukin-12 has been revealed to be a key regulator of the immune response, particularly that involving CTL and NK cells. We report herein the anti-angiogenesis effect of IL-12 on human as well as murine tumors in NK-depleted SCID mice using fibroblasts genetically engineered to secrete this cytokine. Although the in vitro growth of tumor cells was not affected by the presence of IL-12, co-inoculation of IL-12 secreting fibroblasts strongly inhibited tumor growth in immunodeficient mice. The neovascularization surrounding the tumor was remarkably inhibited in the area where the IL-12 secreting fibroblasts were implanted, resulting in the suppression of tumor growth. Lectin staining in tumor sample sections also showed a significant reduction in the number of vessels. The RNA expression of IFN-γ and its inducible antiangiogenic chemokine IP-10 was stimulated in endothelial cells cultured with IL-12. It was also found that IL-12 downregulated the expression of the endothelial cell mitogens VEGF and bFGF.The anti-tumor effects of IL-12 were accompanied by interesting histological changes consisting of a high degree of keratinization and apoptosis and a decrease in the proliferation rate of human tumors and extensive necrosis in the murine ones. Therefore, IL-12 is the candidate gene for this gene gun system.
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Research Products
(20 results)
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[Publications] Mori, Y., Matsunaga, M., Abe, T., Fukushige, S., Miura, K., Sunamura M., Shiiba, K., Nukiwa, T., Sato, M., Horii, A.: "Chromosome band 16q24 is frequently deleted in human gastric cancer."Br.J.Cancer. 80. 556-562 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Matsumoto G., Sunamura M., Shimamura H., Kodama T., Hashimoto W., Kobari M., Kato K., Takeda K., Yagita H., Okumura K., Hamada H., Matsuno S.: "Adjuvant immunotherapy using genetically engineered interleukin 12 secreting fibroblasts prevents recurrence after surgical resection of established tumors in a murine adenocarcinoma model."Surgery. 125. 257-264 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Abe T., Makino N., Furukawa T., Ouyang H., Kimura M., Yatsuoka T., Yokoyama T., Inoue H., Fukushige S., Hoshi M., Hayashi Y., Sunamura M., Kobari M., Matsuno S.Horii A.: "Identification of three commonly deleted regions on chromosome arm 6q in human pancreatic cancer."Genes Chromosom. Cancer. 25. 60-64 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Furukawa, T., Youssef, E.M.., Yatsuoka, T., Yokoyama, T., Makino, N., Inoue, H., Fukushige, S., Hoshi, M., Hayashi. Y., Sunamura M., and Horii, A.: "Cloning and characterization of the human UDP-N-acetylglucosamine : a-1, 3-D-mannoside b-1, 4-N-acetylglucosaminyltransferase IV-homologue (GnT-IV-H) gene."J Hum Genet. 44. 394-401 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Sunamura M., Sun L., Lozonschi L., Duda D.G., Kodama T., Matsumoto G., Shimamura H., Takeda K., Kobari M., Hamada H., Matsuno S.: "The anti-angiogenesis effect of IL-12 during early growth of human pancreatic cancer in SCID mice."Pancreas. 20. 227-233 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Yatsuoka T., Sunamura M., Kimura M., Egawa S., Furukawa T.. Fukushige S., Abe T., Yokoyama T., Inoue H., Shibuya K., Takeda K., Kobari M., Matsuno S., Horii A.: "Association of poor prognosis and loss of 12q, 17q, and 18q and concordant loss of 6q/17p and 12q/18q in human pancreatic ductal adenocarcinoma."Am J Gastroenterol.. 95. 2080-2085 (2000)
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「研究成果報告書概要(欧文)」より
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